The study´s findings show one of the world´s smallest predators, the soil bacteria Myxococcus xanthus, uses a wave formula to spread, engulf and devour other bacteria.

Featured on the cover of this month´s online issue of the journal PLOS Computational Biology, this study explains how the simple motions of individual bacteria are amplified within the larger colony, forming a millions-strong wave that moves outward, seemingly in unison.

"When the cells at the edge of the colony are moving outward, they are unlikely to encounter another Myxococcus xanthus cell, so they keep moving forward," said lead author Oleg Igoshin, assistant professor of bioengineering at Rice. "When they are traveling the other way, back toward the rest of the colony, they are likely to encounter other cells of their kind, and when they pass beside one of these and touch, they get the signal to turn around."

Igoshin said the net effect is that the cells "spend more time moving outward than inward, and as a result, they spread faster."

Myxococcus xanthus is an oft-studied model organism in biology but, Igoshin said, it is one of the few well-studied organisms that lends itself to the study of systems biology, a rapidly growing field of life sciences that aims to model and discover emergent phenomena -- like the rippling waves of Myxococcus xanthus colonies -- that have a basis in genetics but only become apparent when cells cooperate.

"Most of the model bacteria that biologists selected for study in the lab were chosen because they were very good at growing on their own in a test tube and not sticking to the wall or to one another," Igoshin said. "When we were choosing model organisms, we lost a lot of the social properties that systems biologists like to study. Myxococcus xanthus is different in that people chose to study it because it grew into cool patterns and structures arising from cooperative behavior."

Igoshin, a computational biologist, specializes in and focuses on creating mathematical models that can accurately describe the behavior of living organisms. His models are essential in understanding, at a cellular and genetic level, the basis of emergent phenomena.

In the case of Myxococcus xanthus waves, Igoshin and Rice graduate student Haiyang Zhang and postdoctoral fellow Peng Shi created an agent-based model, a computer program that simulated the actions and interactions of individual cells to examine how they collectively produced Myxococcus xanthus waves.

The model showed that just three ingredients were needed to generate the rippling behavior:

- When two cells moving toward one another have side-to-side contact, they exchange a signal that causes one of them to reverse.

- A time interval after each reversal during which cells cannot reverse again.

- Physical interactions that cause the cells to align.

To verify the model's accuracy, Igoshin's team partnered with UTHealth's Heidi Kaplan, associate professor of microbiology and molecular genetics. Kaplan and graduate students Zalman Vaksman and Douglas Litwin, both of the University of Texas Graduate School of Biomedical Sciences at Houston, used time-lapse images from microscopes to examine the behavior of Myxococcus xanthus waves. The experiments confirmed the relationships between wavelength, reversal time and cell velocity that had been predicted by the model.

"We also found an interesting flip side for the behavior, which was counterintuitive and unexpected," Kaplan said. "The same behavior that causes the waves to spread quickly and to cover newly found prey also allows Myxococcus xanthus cells to stay on a patch of food and not drift away until the food is devoured."

While the study was able to observe the wave action of the bacteria, the biochemical process necessary for the individual bacteria to signal one another to reverse from one another is still shrouded in mystery. Often, with bacteria, physical contact is not necessary to convey a signal. But with this study, researchers found that the act of reversing course did require contact between the cells.

"If the mechanism for this behavior can be found, it could prove useful for synthetic biologists who are interested in programming touch-induced functions into synthetic organisms," Igoshin said.

Igoshin´s computer modeling was performed on three National Science Foundation supercomputers that are jointly managed and operated by Rice´s Ken Kennedy Institute for Information Technology and Rice´s Department of Information Technology. Financial support for the study was provided by the National Science Foundation.